IMMUNE EVASION BY HUMAN PAPILLOMAVIRUS

人乳头瘤病毒的免疫逃避

• 批准号: 6487286
• 负责人: Dennis J. McCance
• 金额: $ 15万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6487286
• 关键词: CD40 molecule; Langerhans' cell; MHC class I antigen; T lymphocyte; cell differentiation; chemotaxis; clinical research; cytokine; dendritic cells; human papillomavirus; human subject; keratinocyte; microorganism immunology; protein biosynthesis; transfection; virus infection mechanism; virus protein

Human papillomaviruses (HPV) infect and replicate in stratified epithelial cells of the skin and mucosal surfaces where they can cause benign lesions, or pre-malignant and malignant disease. The papillomaviruses can therefore by divided into low and high risk types depending on their pathology. A common feature of both groups is their ability to persist in the host without stimulating any effective immune response, so that lesions persist for months or even years. Regression does, however, occur spontaneously and is immunogically mediated.. The natural history of infection suggests that the virus has evolved mechanisms to impair an effective immune response from being generated by the host. The host cell of the virus is the keratinocyte, have evidence that the E6 proteins of HPV type 16 inhibits the production of cytokines produced by keratinocytes and so may inhibit stimulation of an effective immune response. In this project we wish to expand these initial observations to determine if other HPV types modulate stimulatory or inhibitory cytokines and to investigate if keratinocytes expressing HPV genes change the functional properties of skin dendritic cells, so that they can no longer stimulate an effective immune response.

人乳头瘤病毒（HPV）在皮肤和粘膜表面的分层上皮细胞中感染并复制，它们可能引起良性病变，或者恶性和恶性疾病。因此，乳头瘤病毒可以通过根据病理学分为低风险和高风险类型。两组的一个共同特征是它们能够在宿主中持续存在而不会刺激任何有效的免疫反应，从而使病变持续数月甚至数年。然而，回归确实是自发发生的，并且是免疫介导的。感染的自然史表明，该病毒已经发展了机制，以损害宿主产生的有效免疫反应。病毒的宿主细胞是角质形成细胞，有证据表明，HPV 16型的E6蛋白抑制了角质形成细胞产生的细胞因子的产生，因此可能抑制刺激有效的免疫反应。在该项目中，我们希望扩大这些初始观察结果，以确定其他HPV类型是否调节刺激性或抑制性细胞因子，并研究表达HPV基因的角质形成细胞是否改变了皮肤树突状细胞的功能性能，以便它们不再能刺激有效的免疫反应。